Fully functionalized small-molecule probes for integrated phenotypic screening and target identification.

ABSTRACT: Phenotypic screening offers a powerful approach to identify small molecules that perturb complex biological processes in cells and organisms. The tendency of small molecules, however, to interact with multiple protein targets, often with moderate to weak affinities, along with the lack of straightforward technologies to characterize these interactions in living systems, has hindered efforts to understand the mechanistic basis for pharmacological activity. Here we address this challenge by creating a fully functionalized small-molecule library whose membership is endowed with: (1) one or more diversity elements to promote interactions with different protein targets in cells, (2) a photoreactive group for UV light-induced covalent cross-linking to interacting proteins, and (3) an alkyne hand

SUBMITTER: Cisar JS 

PROVIDER: S-EPMC3426452 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature